Consent

Objectives

Assess the effectiveness of inhaled corticosteroid (ICS) combinations for long term asthma control and exacerbations.

Background

Asthma is a condition that afflicts almost 9 million children in the United States each year. It is the leading cause of pediatric hospitalization and school absenteeism and is characterized by symptoms of wheezing, coughing, and shortness of breath. There is no cure for asthma but symptoms are typically managed with inhaled corticosteroids as a preventative medication and albuterol as a rescue medication.

Subjects

288 pediatric participants, ages 6 to 18 were enrolled in this study. They were eligible if they had a history of mild persistent asthma but kept the symptoms adequately controlled 4 weeks prior to study entry. Mild persistent asthma for this study was defined as symptoms occurring more than 2 days per week, needing to use albuterol for symptoms for more than 2 days per week, or having more than 2 night-time awakenings per month when not using a controller medication such as an inhaled corticosteroid. Participants were also required to meet one of the following criteria: no previous use of a controller treatment and with a history of 1 to 2 exacerbations in the previous year, treatment for the previous 8 weeks with a monotherapy other than inhaled corticosteroids, or their illness was controlled for the previous 8 weeks on low-dose corticosteroids as monotherapy (≤160 µg daily with a beclomethasone equivalent).

Participants were ineligible if their prebronchodilator forced expiratory volume in 1 second (FEV1) was less than 60% predicted at the first visit; had a history of hospital admission for asthma in the previous year; had any asthma exacerbation in the previous 3 months or more than two in the previous year; had a history of life-threatening asthma exacerbations that required intubation or mechanical ventilation, or that resulted in a hypoxic seizure.

Design

TREXA was a 44-week randomized, double-blind, four-treatment trial with 4 weeks designated as a run-in period. During the run-in period participants received one puff of beclomethasone dipropionate twice daily and rescue treatment containing a placebo inhaler added to rescue albuterol. Participants whose symptoms remained well controlled during the run-in period could continue in the study.

The study had a two by two factorial design where participants were assigned to one of four possible groups:
• Combined group: took ICS twice a day and ICS plus albuterol as rescue medication
• Daily beclomethasone group: took ICS twice a day and placebo ICS plus albuterol as rescue medication
• Rescue beclomethasone group: took placebo ICS twice a day and ICS plus albuterol as rescue medication
• Placebo group: took placebo ICS twice a day and placebo ICS plus albuterol as rescue medication

Twice daily beclomethasone treatment was one puff of beclomethasone (40 µg per puff) or placebo given in the morning and evening. Rescue beclomethasone treatment was two puffs of beclomethasone or placebo for each two puffs of albuterol (180 µg) needed for symptom relief.

The primary outcome measure was the time to first exacerbation that required treatment with prednisone. Exacerbations were defined as the use of more than 12 puffs of albuterol in 24 hours (excluding preventive use before exercise), a peak expiratory flow of less than 70% of reference value before each albuterol use, symptoms that led to inability to sleep or do daily activities for 2 or more consecutive days, a peak expiratory flow of less than 50% of reference value despite relief treatment, or an emergency room visit because of worsening of asthma symptoms.

Conclusions

The frequency of exacerbations was lower in the daily, combined, and rescue groups when compared to the placebo group. Based on this finding, daily inhaled corticosteroids is regarded as a more effective treatment for mild persistent asthma than treatment with albuterol alone. Also, for children with well controlled mild asthma, ICS with albuterol as a rescue medication may be an effective long term treatment while avoiding side effects associated with daily ICS treatment.

Resources Available

Study Documents

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